Combined lipase deficiency (cld/cld) in mice is characterized by marked functional deficiencies of both lipoprotein lipase and hepatic lipase. We used immunocytochemistry to locate intracellular lipoprotein lipase in cultured brown adipocytes derived from cld/cld mice and their unaffected littermates. Unaffected brown adipocytes treated with monensin, which inhibits glycoprotein transport from Golgi, accumulated lipoprotein lipase within the Golgi complex. In contrast, cld/cld brown adipocytes contained intracellular lipoprotein Lipase distributed in a reticular pattern throughout the cell and this distribution was not altered by monensin treatment. Electron microscopic immunoperoxidase studies showed that lipoprotein lipase was present within the endoplasmic reticulum of cld/cld brown adipocytes. These studies indicate the cld/cld cells synthesize a lipase which accumulates in endoplasmic reticulum and is not transferred to Golgi for further modification. This defect in intracellular processing of lipoprotein lipase results in the inability of cld/cld brown adipocytes to secrete the enzyme. Type C Niemann Pick (NP-C) disease is an autosomal-recessive neurovisceral lipid storage disorder. Fibroblasts derived from patients with this disease incubated with LDL accumulated intracellularly excessive amounts of unesterified cholesterol. Cytochemical techniques revealed that this abnormal cholesterol accumulation is associated not only with storage of cholesterol in lysosomes but with cholesterol enrichment of the Golgi complex. These findings indicate that components of the Golgi complex play a role in the intracellular translocation of exogeneously derived cholesterol and that disruptions of the cholesterol transport pathway at the Golgi may be responsible for the deficiency in cholesterol utilization by NP-C fibroblasts.